The mainstay treatments of failure-to-store bladder are the muscarinic anticholinergic agents (Table 10.1), which can be given in either short-acting or long-acting formulations. Nonselective antimuscarinics include oxybutynin, tolterodine, trospium, and fesoterodine. The M2- or M3-antimuscarinics, darifenacin and solifenacin, are more selective for cholinergic receptors in the bladder, thereby reducing systemic toxicity. Adverse effects of antimuscarinics include dry mouth, constipation, and delirium. These medications should be avoided in patients with cognitive dysfunction, narrow-angle glaucoma, and structural bladder output obstruction.

Patients who are intolerant of anticholinergic agents may benefit from detrusor muscle botulinum toxin (BTX)-A injections. Intranasal desmopressin (DDAVP) may be helpful to control nocturia but can produce hyponatremia, requiring monitoring of serum sodium and osmolality.

Patients with failure-to-empty bladder are at increased risk for UTI, renal dysfunction, and nephrolithiasis due to stagnation of urinary flow. This is usually best managed with sterile intermittent straight catheterization (ISC), performed several times daily. If urinary urgency and urge incontinence persist in the interval between ISCs, then an anticholinergic agent can be added. Low-dose antibiotics (nitrofurantoin) or urinary-acidifying agents (vitamin C) are often recommended in conjunction with ISC to reduce the incidence of UTI. Patients who cannot perform ISC due to difficulty with manual dexterity or lower extremity spasticity, or who are uncomfortable performing ISC, may benefit from an α-2-adrenergic blocking agent such as tamsulosin, which relaxes the external urinary sphincter, allowing for more effective bladder emptying. An algorithm demonstrating the management of patients with bladder dysfunction in MS is presented in Figure 10.1.

Bowel dysfunction

Bowel disorders are common in MS. Constipation, fecal incontinence, or both occur in 29% to over 50% of individuals with MS. In one survey of 155 patients with MS, 34% spent more than 30 min daily managing their bowel symptoms, and bowel dysfunction was rated as equally disabling as mobility impairment.

The pathophysiology of bowel dysfunction in MS is primarily due to disruption of cerebral and spinal cord pathways that modulate gastrointestinal transit, pelvic floor muscle tone, anorectal autonomic and sensory function, and volitional motor control of the external anal sphincter. Constipation in MS is further exacerbated by physical immobility and the use of anticholinergic agents for concomitant neurogenic bladder.

Management of MS-associated constipation typically relies on conservative strategies, such as timed bowel elimination, maintenance of physical activity and hydration, and use of stool-bulking agents and dietary fiber. Medical therapies include stool softeners, rectal stimulants (polyethylene glycol or bisacodyl suppositories), laxatives, and enemas. Lubiprostone, a bowel-motility agent, is currently under investigation as a potential treatment for MS-associated constipation.

Fecal incontinence may occur as a result of stool impaction, which can be corrected with manual disimpaction and anticonstipation measures. Fecal incontinence associated with urgency is best addressed with anticholinergic agents. In addition, biofeedback has also been reported to ameliorate both constipation and fecal incontinence in patients with MS.

Sexual dysfunction

SD in patients with MS is common, affecting up to 50–73% of men and 40–70% of women with MS. The causes of SD in MS are multifactorial, including neuroanatomic disruption due to demyelinating lesions in the spinal cord, pons, and cerebral hemispheres (primary or neurogenic SD); interference of sexual activity due to MS-associated disability, such as spasticity, fatigue, cognitive dysfunction, neurogenic bladder, and pain (secondary SD); and disturbances due to psychologic and emotional complications of MS (tertiary SD). Finally, many agents used to manage MS symptoms, such as anticholinergics for bladder dysfunction, antispasticity medications, and selective serotonin reuptake inhibitors (SSRIs) for depression, may produce SD.

Symptoms of SD in men with MS include reduced libido, erectile dysfunction (ED), and ejaculatory–orgasmic disturbances. Women with MS also complain of reduced libido, as well as decreased vaginal lubrication, abnormal vaginal sensation, anorgasmia, and dyspareunia. SD can occur early in the MS disease course and impacts adversely on quality of life. Unfortunately, many patients are reluctant to discuss sexual complaints with their neurologist, and the physician may also be uncomfortable in discussing symptoms of SD. Thus, SD may be underreported in the MS population. Screening for SD is recommended at the initial patient visit and during follow-up examinations. Validated self-administered tools, such as the MS Intimacy and Sexuality Questionnaire-19 (MSISQ-19), may be useful for this purpose.

Neurogenic ED in men with MS may be effectively treated with phosphodiesterase-5 (PDE-5) inhibitors, including sildenafil, vardenafil, and tadalafil (Table 10.1). PDE-5 inhibition produces smooth muscle relaxation, resulting in reduced penile venous return and sustained erection. In a randomized, placebo-controlled study of 217 men with MS and ED, sildenafil citrate in doses from 25 to 100 mg significantly improved both ED (89% vs. 24%, p < 0.001) and quality of life compared with placebo. Adverse effects of sildenafil were mild and consisted of headache, flushing, and dyspepsia, none of which resulted in drug discontinuation. In another controlled study of sildenafil in 203 men with MS and ED, the overall benefit of sildenafil on ED compared with placebo was less robust (32.8% vs. 17.6%, p < 0.04). Cardiovascular events occurred in three patients. Although vardenafil and tadalafil have not been specifically studied in MS, anecdotal evidence supports their effectiveness. It is important to emphasize the PDE-5 inhibitors are contraindicated in patients using nitrates for coronary artery disease (Table 10.2).

Nonpharmacologic approaches for ED can be considered for patients whose symptoms are refractory to PDE-5 inhibitors or for whom adverse drug effects are intolerable. These include intracavernous vasodilator agents (e.g., papaverine, alprostadil) and vacuum-based penile prostheses.

There is no established medical therapy for SD in women with MS. In one double-blind, placebo-controlled, crossover study of 19 females with MS-associated SD, sildenafil failed to demonstrate significant benefit, although there was some improvement in vaginal lubrication in the sildenafil group. Treatment of SD in women with MS relies mostly on nonpharmacologic modalities. Vaginal lubricants may be useful to enhance perineal sensation and ameliorate vaginal dryness. Topical estrogen may be helpful for vaginal dryness and dyspareunia in women who are postmenopausal. External vibratory stimulation of the vagina and clitoris may augment physiologic vasocongestion and orgasm.

Treatment of secondary SD in both men and women with MS is directed at ameliorating MS-related symptoms impairing sexual function, such as spasticity, pain, and fatigue. Premedication with agents directed at these specific symptoms before sexual activity may reduce their impact on sexual function.

Tertiary SD in both men and women with MS, typically manifested by reduced libido, is associated with the psychosocial consequences of chronic illness, including mood dysfunction, negative self-image, and fear of rejection. Clinical depression is present in over 50% of MS patients during the course of their disorder. Treatment of depression, which is discussed in another chapter of this book, whether pharmacologically or with cognitive behavioral therapy, can improve tertiary SD. Unfortunately, the commonly used SSRIs for depression may themselves produce adverse effects on sexual function; bupropion produces less SD and may be more useful in patients whose SD is thought to be in part due to SSRI therapy.

It is important to emphasize that effective treatment of SD in patients with MS requires a multidisciplinary approach, involving the neurologist, MS nurse specialist, and mental health therapist. These resources may be best provided by a tertiary MS clinic.